The regulation and integration of bile acid and cholesterol synthesis in normal, preneoplastic, and neoplastic hepatocytes is being studied in vivo and in an isolated liver cell culture system by perturbing the rate controlling enzymes for both metabolic pathways, cholesterol 7 alpha-hydroxylase and HMG CoA reductase in precise ways. Special emphasis is being given to developing techniques for maintaining cells from hyperplastic nodules in vitro and to using drugs such as colchicine and Triton WR 1339 that alter cholesterol synthesis and serum lipoproteins in reproducible ways. The role of hormones in modulating the feedback control of cholesterol synthesis in normal hepatocytes and the loss of this control in transplantable hepatomas will be studied in rats subjected to endocrine ablation and in isolated hepatocyte cell culture systems.